The proposed project attempts to define biologically, genetically, diagnostically and therapeutically distinct subgroups of the schizophrenic-like illnesses. Recent studies have suggested that bimodal distributions of certain key biological findings occur in schizophrenic populations; unimodal distributions of similar parameters occur in control populations. These biologic bimodalities (platelet MAO, growth hormone response to apomorphine and perhaps platelet PGE1 stimulated adenylate cyclase activity) will provide the basis for investigations of differential genetic, diagnostic and treatment response groups. More specifically, each of 40 patients diagnosed as schizophrenia or schizoaffective disease will undergo biological testing on the parameters noted above, will receive diagnostic assessment according to several currently used diagnostic instruments and will undergo a therapeutic trial with lithium. First degree relatives of such patients will be studied for evidence of affective or schizophrenic symptomatology. Data analysis will determine whether a subgroup of the schizophrenic population can be defined which manifests characteristic abnormalities by biologic testing, which have genetic history of affective disease, which can be distinctly diagnosed clinically and which respond to lithium. Such a group would be contrasted to a second group of schizophrenic-like illnesses which show differing biologic patterns, which have evidence of schizophrenic illness in their family, which can be distinguished by specific diagnostic parameters and which fail to respond to lithium. The delineation by multivariate analysis of such subgroups of the schizophrenic population is the goal of the proposed work.